The Ras oncogene mediates a variety of biological effects that promote tumorigenic transformation. However, activated forms of Ras also have a surprising number anti-transformation aspects. They can induce senesence, cell cycle arrest, and even death by apoptosis. The mechanisms behind these anti-neoplastic effects remain poorly understood. We have identified a family of novel Ras effectors which appear to mediate some of the anti-neoplastic activities of Ras. especially apoptosis. We have now determined that at least three members of this family exhibit all the classic hallmarks of Ras effectors yet also demonstrate the properties of tumor suppressors. Namely, they mediate inhibition of cell growth and transformation and are frequently down-regulated by epigenetic mechanisms during tumor development. We now have preliminary data that two other members of this family have similar properties. Thus, we have identified and partially characterized a novel class of Ras-activated tumor suppressor. We are currently investigating the mechanism of action of these proteins.